The incidence and mortality of lung cancer continue to rise and attempts at early diagnosis to improve prognosis appear to have increased overall five year survivals to no more than 15-20%. We propose that the pathogenesis of lung cancer occurs as a progressive pattern of bronchial epithelial atypias extending over a period of 10-20 years, with the first step being squamous metaplasia followed, in turn, by mild, moderate and severe epithelial atypia and culminating in carcinoma. We believe that by periodic cytologic sputum examination, individuals who are at high risk for development of lung cancer can be identified and counseled regarding cessations of smoking, transferred to a less hazardous occupational environment, and possibly treated with retinoids to prevent further progression of their bronchial atypias. This study is focused on the precise identification of premalignant changes in pulmonary epithelial cells in sputum, not on mass screening for the early diagnosis of established pulmonary cancers. Our hypothesis is that computer-assisted morphometric analysis can assist in these tedious, labor intensive searches. To realize these objectives, it is imperative that definitive objective morphometric criteria be established for the identification of the atypical bronchial epithelial cells in sputum. To develop these criteria we are using various image processing techniques coupled with cell image analysis. Results obtained to date show that the degree of cell alterations in bronchial epithelial atypia can be accurately monitored by computerized cell image analysis.